RESUMEN
Periodontitis, an inflammatory bone resorption disease associated with dental plaque, poses significant challenges for effective treatment. In this study, we developed Mino@ZIF-8 nanoparticles inspired by the periodontal microenvironment and the unique properties of zeolitic imidazolate framework 8, aiming to address the complex pathogenesis of periodontitis. Transcriptome analysis revealed the active engagement of Mino@ZIF-8 nanoparticles in innate and adaptive inflammatory host defense and cellular metabolic remodeling. Through sustained release of the anti-inflammatory and antibacterial agent minocycline hydrochloride (Mino) and the generation of Zn2+ with pro-antioxidant effects during degradation, Mino@ZIF-8 nanoparticles synergistically alleviate inflammation and oxidative damage. Notably, our study focuses on the pivotal role of zinc ions in mitochondrial oxidation protection. Under lipopolysaccharide (LPS) stimulation, periodontal ligament cells undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis, leading to reduced ATP production and increased reactive oxygen species levels. However, Zn2+ effectively rebalances the glycolysis-OXPHOS imbalance, restoring cellular bioenergetics, mitigating oxidative damage, rescuing impaired mitochondria, and suppressing inflammatory cytokine production through modulation of the AKT/GSK3ß/NRF2 pathway. This research not only presents a promising approach for periodontitis treatment but also offers novel therapeutic opportunities for zinc-containing materials, providing valuable insights into the design of biomaterials targeting cellular energy metabolism regulation.
RESUMEN
Regeneration of bone tissue in the environment of diabetes mellitus (DM) remains one of the clinical challenges, with malfunction of stem cells in a high-glucose microenvironment being the primary obstacle. We designed an injectable sustained-release PDGF-BB nanocomposite hydrogel. PDGF-BB, a star molecule for treating various complications of DM, was used for the first time for DM-associated bone regeneration, and we showed that it restored stem cell proliferation and migration and facilitated osteogenesis inhibition under high glucose stimulation by activating ERK and AKT pathways. To address the requirements for continuous PDGF-BB release in GelMA while also increasing mechanical strength, nanoclay LAPONITE® was added, which may still exhibit pro-osteogenic activity in diabetic environments by releasing bioactive ions (Si4+, Mg2+, and Li+). This injectable hydrogel heals calvarial lesions successfully in diabetic rats and has the potential to be used as a direct and effective tool for treating diabetic patients.
